1431697-78-7
1431697-78-7 structure
- Name: CAL-130 Hydrochloride
- Chemical Name: CAL-130 Hydrochloride
- CAS Number: 1431697-78-7
- Molecular Formula: C23H23ClN8O
- Molecular Weight: 462.935
- Catalog: Research Areas Cancer
- Create Date: 2018-05-19 12:24:54
- Modify Date: 2024-01-09 15:08:48
-
CAL-130 is a PI3Kδ and PI3Kγ inhibitor with IC50s of 1.3 and 6.1 nM, respectively.
| Name | CAL-130 Hydrochloride |
|---|---|
| Synonyms |
2-{(1S)-1-[(2-Amino-9H-purin-6-yl)amino]ethyl}-5-methyl-3-(2-methylphenyl)-4(3H)-quinazolinone hydrochloride (1:1)
4(3H)-Quinazolinone, 2-[(1S)-1-[(2-amino-9H-purin-6-yl)amino]ethyl]-5-methyl-3-(2-methylphenyl)-, hydrochloride (1:1) CAL-130 (Hydrochloride) |
| Description | CAL-130 is a PI3Kδ and PI3Kγ inhibitor with IC50s of 1.3 and 6.1 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
p110δ:1.3 nM (IC50) p110γ:6.1 nM (IC50) p110β:56 nM (IC50) p110α:115 nM (IC50) |
| In Vitro | CAL-130 preferentially inhibits the function of both p110γ and p110δ catalytic domains. IC50 values of CAL-130 are 1.3 and 6.1 nM for p110δ and p110γ, respectively, as compared to 115 and 56 nM for p110α and p110β. CAL-130 does not inhibit additional intracellular signaling pathways (i.e., p38 MAPK or insulin receptor tyrosine kinase) that are critical for general cell function and survival[1]. |
| In Vivo | The clinical significance of interfering with the combined activities of PI3Kγ and PI3Kδ is determined by administering CAL-130 to Lck/Ptenfl/fl mice with established T cell acute lymphoblastic leukemia (T-ALL). Candidate animals for survival studies are ill appearing, have a white blood cell (WBC) count above 45,000 μL-1, evidence of blasts on peripheral smear, and a majority of circulation cells (>75%) staining double positive for Thy1.2 and Ki-67. Mice receive an oral dose (10 mg/kg) of CAL-130 every 8 hr for a period of 7 days and are then followed until moribund. Despite the limited duration of therapy, CAL-130 is highly effective in extending the median survival for treated animals to 45 days as compared 7.5 days for the control group[1]. |
| Kinase Assay | IC50 values for CAL-130 inhibition of PI3K isoforms are determined in ex vivo PI3 kinase assays using recombinant PI3K. A ten-point kinase inhibitory profile is determined with ATP at a concentration consistent with the KM for each enzyme[1]. |
| Cell Assay | Cell proliferation of CCRF-CEM cells or shRNA-transfected CCRF-CEM cells, in presence or absence of CAL-130 (1, 2.5 and 5 μM), is followed by cell counting of samples in triplicate using a hemocytometer and trypan blue. For apoptosis determinations of untransfected or shRNA-transfected CCRF-CEMs, cells are stained with APC-conjugated Annexin-V in Annexin Binding Buffer and analyzed by flow cytometry. For primary T-ALL samples, cell viability is assessed using the BD Cell Viability kit coupled with the use of fluorescentcounting beads. For this, cells are plated with MS5-DL1 stroma cells, and after 72 hr following CAL-130 treatment, cells are harvested and stained with an APC-conjugated antihuman CD45 followed by a staining with the aforementioned kit[1]. |
| Animal Admin | Mice[1] For subcutaneous xenograft experiments, luminescent CCRF-CEM (CEMluc) cells are generated by lentiviral infection with FUW-luc and selection with Neomycin. Luciferase expression is verified with the Dual-Luciferase Reporter Assay kit. 2.5×106 CEM-luc cells embedded in Matrigel are injected in the flank of NOD.Cg-Prkdcscid Il2rgtm1Wjl/Sz mice. After 1 week, mice are treated by oral gavage with vehicle (0.5% methyl cellulose, 0.1% Tween 80), or CAL-130 (10 mg/kg) every 8 hr daily for 4 days, and then tumors are imaged as follows: mice anesthetized by isoflurane inhalation are injected intraperitoneally with D-luciferin (50 mg/kg). Photonic emission is imaged with the in vivo imaging system. Tumor bioluminescence is quantified by integrating the photonic flux (photons per second) through a region encircling each tumor using the Living Image software package. Administration of D-luciferin and detection of tumor bioluminescence in Lck/Ptenfl/fl/Gt(ROSA)26Sortm1(Luc)Kael/J mice are performed in a similar manner. |
| References |
| Molecular Formula | C23H23ClN8O |
|---|---|
| Molecular Weight | 462.935 |
| Exact Mass | 462.168335 |
| Storage condition | 2-8℃ |